Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

Abstract

Abstract-To obtain detailed information concerning the effects of different vaso dilators on venous return, experiments were carried out on 28 dogs by the use of the open-loop method. Blood from the superior and inferior venae cavae was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant flow rate. Changes in reservoir volume reflected a total blood shift from the experimental dog and indicated changes in venous return. Drugs were administered into the ascending aorta. Nitroglycerin (1-10 pg/kg) decreased systemic blood pressure, total peripheral resistance and venous return but scarcely altered heart rate. Trimetazidine (0.3-3 mg/kg) decreased systemic blood pressure, total peripheral resistance, venous return and heart rate. Verapamil (10-100 ug/kg) decreased systemic blood pressure, total peripheral resistance and heart rate, and increased venous return. SK&F 24260 (1-10 fig/kg) decreased systemic blood pres sure, total peripheral resistance and increased venous return. Only high doses (10 30 pg/kg) of SK&F 24260 reduced heart rate. Rigorous measurements of systemic output showed that nitroglycerin (10 pg/kg), trimetazidine (3 mg/kg), verapamil (100 pg/kg), SK&F 24260 (10 pg/kg) produced no change in this parameter. SK&F 24260 increased venous return even when sino-aortic baroreceptor reflex was eliminated, ruling out reflex venoconstriction as a possible cause of the increased venous return. The results suggest the following: [1] Vasodilators like SK&F 24260 and verapamil increase venous return by decreasing arterial and/or venous resistance. [2] If the effect which increases venous capacitance prevails over the effect which decreases ar terial and/or venous resistance, venous return is reduced as is the case of nitroglycerin and trimetazidine.Nitroglycerin reduces the left ventricular end-diastolic pressure and volume (1-4), and such is considered to be one of mechanisms responsible for the antianginal action of nitro glycerin (1, 2, 4-6). The reduction in these 2 parameters is thought to be due mainly to a decrease in venous return (3, 4). Thus, it was of interest to investigate the effect on venous return of other vasodilators used for prevention of attacks of angina pectoris. In previous studies (7,8) we demonstrated that some of vasodilators increased venous return whereas others decreased it. However, in those studies we measured venous return by noncannulating type flow probes of electromagnetic flow meters placed at the superior and the inferior vena cava in anesthetized open-chest dogs and did not control cardiac input (the closed-loop method). Thus, it was hardly discernible whether the observed change in venous return by a certain vasodilator would be due to its effect on vasculature or on the heart. Most

Cardiohemodynamic effects of cromakalim and pinacidil, potassium-channel openers, in the dog, special reference to venous return

“…Even verapamil, whose cardiodepressant action became manifest in vasodilator doses and which only reduced venous return and CO in closed-loop preparations [17], increased venous return in open-loop preparations of dogs in which the cardiac input was controlled, when administered into the ascending aorta so as to minimize the effects on the heart [22]. We ascribed the decreased venous return and CO produced by the highest doses of cromakalim and pinacidil to decreased cardiac contractility.…”

Inhibitory Effect of Trimetazidine on Utilization of Myocardial Glycogen during Coronary Ligation in Dogs

“…Firts. trimetazidine inhibits the ischemia-induced al terations, because it decreases the oxygen consumption of the heart as a result of a decrease in venous return to the heart [Jmai et al, 1977;Taira et al, 1980], In the present study, however, we did not measure the oxy gen consumption of the heart, and therefore it is uncertain whether or not this view is cor rect. However, according to the hemody namic data of the present study, trimetazidine did not have a marked effect on blood pressure and heart rate, suggesting that trimetazidine may not have a marked influence on the oxygen consumption of the heart.…”

Effects of anipamil on cardiovascular status and regional blood flow in anaesthetized rats

“…Mean circulatory filling pressure is a measure of total body venous tone (Guyton et al, 1973). An increase in venous return after verapamil (Taira et al, 1980) or nifedipine (Ogilvie, 1985) has also been reported to occur in anaethetised dogs. The suggestion that anipamil caused an increase in cardiac output by increasing venous tone is supported by other reports to the effect that a number of calcium antagonists can increase cardiac output while reducing heart rate (Hof et al, 1982;Flaim & Zelis, 1982).…”